Implanted catheters enjoy widespread use in a number of medical procedures. For example, intravenous (IV) therapy relies on long-term implantation of a venous catheter to deliver fluids, medications, and other substances to a patient. Hemodialysis and hemofiltration both rely on separate draw and return catheters implanted in a vein to allow extracorporeal treatment of the blood. Peritoneal dialysis, in contrast, relies on a single catheter implanted in the peritoneum to permit introduction and withdrawal of dialysate to permit in situ dialysis.
The need to leave catheters implanted over long periods of time raises a number of concerns. For example, the catheters can become infected requiring treatment of the patient and often times removal of the catheter. This is a particular problem with transcutaneous catheters where the skin penetration is a common route of infection. In addition, implanted catheters can often become plugged or fouled over time. This is a particular problem with intravascular catheters where clotting and thrombus formation within the catheter lumen can be problematic.
To reduce problems associated with thrombus formation and to maintain the patency of catheters, it is now common to “lock” catheters between successive uses. Locking typically involves first flushing the catheter with saline to remove blood and other substances from the catheter lumen. After the catheter has been flushed, an anti-coagulant solution, such as heparin, is then injected to displace the saline and fill the lumen. The heparin-locking solution both excludes blood from the lumen and actively inhibits clotting and thrombus formation within the lumen. While some thrombus may still form at the distal tip of the catheter, the formation is usually minimal. It has further been proposed to combine various anti-microbial, bactericidal, or bacteriostatic substances with the locking solution in order to inhibit infection at the same time that thrombus is being inhibited.
While generally effective, the use of heparin locks suffers from a number of disadvantages. The need to prepare a heparin solution at the end of every catheter treatment session is time-consuming and presents an opportunity for a caregiver to commit an error. Hemodialysis and hemofiltration patients will have to undergo such heparin locks at least several times a week, while patients on IV may have to undergo such heparin locks several times a day. Over time, heparin locks are inconvenient and expensive. Moreover, the need to combine a separate anti-microbial agent in the heparin lock solution further complicates the procedure and adds expense, and the addition of an anti-microbial agent to the heparin lock will generally be effective only within the lumen and at the openings from the lumen. There will be little reduction in the risk of infection in the regions surrounding the implanted catheter, including at the point of penetration through the skin where the risk of infection is the greatest.
A lock solution formulation containing ethanol and tri-sodium citrate provides anti-coagulant and disinfection properties. However, catheters made with silicone elastomers, due to their very high moisture and alcohol permeability, as well as catheters made of other permeable materials, could become blocked due to crystallized citrate lodged in some segments of the catheters, causing occlusion.
It would be desirable to improve lock solution formulations containing a lower alcohol and an anti-coagulant, antibiotic, and/or anti-microbial, such as the ethanol tri-sodium citrate formulation, to prevent such blocking while maintaining their performances.